HCID 13868949, compound → HCID 13464760, compound

HRID 1744004Notes

Reaction equation

HRID 1744004 reaction equation
[OH:1][C:2]1[C:12]2[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][C:6]=2[CH:5]=[CH:4][CH:3]=1>C1CCCCCC=1>[O:1]=[C:2]1[C:12]2[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][C:6]=2[CH2:5][CH2:4][CH2:3]1

Participants

3

Reactant 1

HCID 13868949HCID 13868949, compound

Product 1

HCID 13464760HCID 13464760, compoundYield 49.5%

Reagents, catalysts & solvents 1

HCID 12363CyclohepteneSolvent

Procedure

Prepared as in Example 37, using 4-hydroxy-6,7,8,9-tetrahydro-5H-benzocycloheptene as the starting material, which was prepared as follows: 8 g (71.4 mmol) 2-hydroxypyrone (Syn. Commun., 5, 461, (1975)) and 20 mL cycloheptene were reacted in a sealed tube at 150° C. for 24 h to give 1-oxo-3,4,6,7,8,9-hexahydro-5H-benzocycloheptene in 49.5% yield, followed by reaction with isopropenyl acetate to afford the enol acetate and treatment with 2,3-dichloro-5,6-dicyanobenzoquinone at 90° C. for 1.5 h (see J. Med. Chem., 37, 3803 (1994)) to afford 4-acetoxy-6,7,8,9-tetrahydro-5H-benzocycloheptene in 69% yield as an oil. Hydrolysis with 3.7 equivalents of powdered potassium hydroxide in ethanol at room temperature for 2 h gave a 44% yield of the desired 4-hydroxy-6,7,8,9-tetrahydro-5H-benzocycloheptene after purification by column chromatography as a white solid. The remaining steps in the sequence then followed Example 48. The final step proceeded in 89% yield to give the product as an amorphous solid as the hydrochloride salt from ether.

Workup

  1. customPrepared as in Example 37
  2. customwas prepared

Sources & evidence

ORD record
ord-0824732c111e49e4abe36451b8b7b962
Source dataset
uspto-grants-2006_03
Patent number
US07012078B2

Reaction notes

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